Contribution of α₂-adrenoceptors in caudal ventrolateral medulla to cardiovascular regulation in rat

Abstract

The inhibitory action of α2-agonists on the cardiovascular neurons has been elucidated in the rostral ventrolateral medulla (RVLM) but not in the caudal ventrolateral medulla (CVLM). Our study aimed to clarify whether microinjection of clonidine into the CVLM elicits any cardiovascular effect and whether endogenous α2-adrenoceptor-mediated mechanisms contribute to the tonic activity of the CVLM neurons. In male Sprague-Dawley rats (7–9 wk old, 270–320 g) anesthetized with urethan, unilateral microinjection of 8 nmol of clonidine into the CVLM ( n = 10) increased mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) by 12.1 ± 1.8 mmHg (mean ± SE, P < 0.01) and 25.8 ± 4.8% ( P < 0.01), while heart rate (HR) remained unaltered. Unilateral microinjection of 2 nmol of SKF-86466, a selective blocker of the α2-adrenoceptors, into the CVLM ( n = 10) decreased MAP, HR, and RSNA (−11.6 ± 2.6 mmHg, −26 ± 7 beats/min, and −15.3 ± 1.7%, respectively, P < 0.01 for each). Artificial cerebrospinal fluid caused neither a cardiovascular effect nor a sympathetic response. Prior injection of SKF-86466 into the ipsilateral CVLM attenuated the effects of clonidine. Bilateral microinjection of muscimol into the RVLM abolished the effects of both clonidine and SKF-86466 injected into the CVLM. The pressor and sympathoexcitatory effects of clonidine injected into the CVLM suggest a neuroinhibitory action of the drug on the CVLM neurons. In addition,the depressor and sympathoinhibitory effects of SKF-86466 injected into the CVLM indicated that activation of α2-adrenoceptors by endogenous ligand inhibits CVLM neurons. The effects of clonidine and the α2-adrenoceptor antagonist in the CVLM require the integrity of the RVLM.

Hypotensive and sedative effects of clonidine injected into the rostral ventrolateral medulla of conscious rats

“…In the caudal ventrolateral medulla, microinjection of 2 nmol of SKF-86466 decreased MAP and RSNA in urethane-anesthetized rats (33). These previous studies (17,33) suggested that the imidazoline receptor with or without the ␣ 2 -adrenoceptor mechanism in the RVLM and in the caudal ventrolateral medulla tonically regulated blood pressure in urethane-anesthetized rats.…”

“…In urethane-anesthetized spontaneously hypertensive rats, microinjection of 4 nmol of efaroxan, an ␣ 2 -antagonist with relatively higher affinity for I 1 -imidazoline receptors, into the bilateral RVLM increased MAP and HR, whereas 10 nmol of SKF-86466, a selective ␣ 2 -antagonist, did not change baseline MAP and HR (17). In the caudal ventrolateral medulla, microinjection of 2 nmol of SKF-86466 decreased MAP and RSNA in urethane-anesthetized rats (33). These previous studies (17,33) suggested that the imidazoline receptor with or without the ␣ 2 -adrenoceptor mechanism in the RVLM and in the caudal ventrolateral medulla tonically regulated blood pressure in urethane-anesthetized rats.…”

CNS Site of Action and Brainstem Circuitry Responsible for the Intravenous Effects of Nicotine on Gastric Tone

“…The dose of yohimbine used for blocking ␣2 adrenergic receptors was 500 pmol and was selected on the basis of data reported by Sved and colleagues (1992), wherein they evaluated a dose range of 10 -500 pmol of yohimbine on ␣2 adrenergic responses in the N TS and found that 200 pmol was f ully effective as an antagonist of this receptor. The dose of SK F 86466 was 1 nmol and was selected on the basis of data reported by others (Ernsberger et al, 1990;Gomez et al, 1991;Sesoko et al, 1998) in which a dose range of 1-2 nmol of SK F 86466 was used to selectively block ␣2 adrenergic receptors in the ventrolateral medulla.…”

Prototypical Imidazoline-1 Receptor Ligand Moxonidine Activates Alpha2-Adrenoceptors in Bulbospinal Neurons of the RVL

“…This notion can probably be extended to the effect of ␣2-AR agonists in many other brain stem structures that contribute to sympathetic regulation and have a high density of GABAergic receptors (nucleus of the solitary tract, dorsolateral pons, autonomic areas of the thoracic spinal cord). Accordingly, the ␣2-AR agonist clonidine can increase blood pressure, for example, when injected slightly caudal to the RVL in urethan-anesthetized rats (Sesoko et al 1998) or intracerebroventricular in conscious rats. In each case, pharmacological evidence suggests that the pressor effects were caused by ␣2-AR stimulation.…”